Jason Burdick, University of Pennsylvania
Biomaterial Approaches to Endogenous Tissue Repair in the Heart
Written by Jessalyn Low Hui Ying
Cardiac repair following myocardial infarction (MI) is essential to prevent further progression of left ventricular remodeling leading to heart failure. In this talk, Jason Burdick presents his research team’s work on designing biomaterials to improve cardiac tissue repair.
Burdick first explains that to introduce signals for repair, the researchers took the approach of using injectable hydrogels, as they can achieve local and sustained delivery of therapeutics. For this, they designed a hydrogel from hyaluronic acid (HA) using guest-host chemistry, and demonstrated that these hydrogels exhibited shear-thinning and self-healing properties - important properties for introducing hydrogels into the heart. In the treatment of MI, a target for repair is the proliferation of cardiomyocytes, to restore cardiomyocyte loss following heart injury. Thus, the researchers tested using this hydrogel to deliver miR-302 mimics, a microRNA (miRNA)-based therapy. Functional recovery studies showed that injection of gel/miR-302 following MI successfully induced cardiomyocyte proliferation and improved cardiac function.
Burdick next shared that with the knowledge that miRNA therapies work in vivo, the researchers wanted to design in vitro models that can mimic features of MI for better development of therapies. Thus, the approach they took was to use cell-dense tissue models, given the high cellularity of myocardial tissues. This was achieved using a new bioprinting technique which they developed for cell spheroid assembly. Here, single-cell spheroids are deposited to the shear-thinning, self-healing hydrogel, and patterned into the desired organization, after which the hydrogel reforms around the spheroids. This technique was then applied to assembling cardiac spheroids for modeling cardiac tissue. As in the case of MI, healthy and scarred microtissues were designed and it was demonstrated that they could be used to characterize behaviors like contraction and electrophysiology. Heterogenous cardiac tissue models were also designed which comprised both healthy and scarred spheroids. Using this model, it was observed the disruption of calcium signaling, quantified as activation delay, across scarred regions.
Burdick ends this talk explaining how these cardiac tissue models could be used for the screening of therapies, in particular, understanding how to control dose and timing for the presentation of miRNA for cardiac tissue repair. These tissue models could also be used to show cardiomyocyte and fibroblast proliferation in miRNA-treated microtissues.